Further insights into to the role of statins against active tuberculosis: systematic review and meta-analysis

Meregildo-Rodríguez, Edinson Dante; Chunga-Chévez, Eleodoro Vladimir; Gianmarco, Robles-Arce Luis; Vásquez-Tirado, Gustavo Adolfo

doi:10.53854/liim-3002-4

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…There is recent evidence that CCBs, beta-blockers, statins, and oral antidiabetics could act as immunomodulators—by improving the host’s anti-mycobacterial responses—and optimize the effect of anti-tuberculosis drugs or reducing the risk of developing active tuberculosis ( Kristiansen and Amaral, 1997 ; Gupta et al, 2009 ; Gupta et al, 2013 ; Meregildo-Rodriguez et al, 2022a ; Meregildo-Rodriguez et al, 2022b ), which is consistent with our results. Conversely, one systematic review and meta-analysis has reported that some oral antidiabetic drugs, such as DPP-4 inhibitors, could increase the risk of developing tuberculosis in patients with diabetes ( Meregildo-Rodriguez et al, 2022b ).…”

Section: Discussionsupporting

confidence: 92%

“…There is growing interest in utilizing immunomodulators to complement the existing anti-TB drugs by enhancing the host’s anti-mycobacterial responses. Statins, beta-blockers, and calcium channel blockers (CCBs) have been reported as some of the most promising host-directed therapies ( Lee et al, 2015a ; Tahir et al, 2020 ; Dutta et al, 2021 ; Mitini-Nkhoma et al, 2021 ; Meregildo-Rodriguez et al, 2022a ; Cubillos-Angulo et al, 2022 ). Additionally, certain ion channel blockers interfere with the activity of mycobacterial efflux pumps ( Kristiansen and Amaral, 1997 ; Gupta et al, 2013 ; Mitini-Nkhoma et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Effect of calcium-channel blockers on the risk of active tuberculosis and mortality: systematic review and meta-analysis

Meregildo-Rodriguez,

Asmat-Rubio,

Bardales-Zuta

et al. 2024

Front. Pharmacol.

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Introduction: Recent studies suggest that calcium channel blockers (CCBs) could reduce the risk of active tuberculosis and improve clinical outcomes. We aimed to synthesize the evidence regarding the effect of CCBs on the risk of developing active tuberculosis and mortality.Methods: We systematically searched for observational studies and clinical trials published in six databases until 31 August 2023, following a PECO/PICO strategy.Results: We included eight observational studies, 4,020,830 patients, among whom 241,761 had diabetes mellitus and 30,397 had active tuberculosis. According to our results, CCBs reduce the risk of developing active tuberculosis by 29% (RR 0.71; 95% CI 0.67–0.75) in patients with and without diabetes mellitus. However, CCBs do not show any benefit in terms of tuberculosis-related mortality (RR 1.00; 95% CI 0.98–1.02). For both outcomes, no statistical heterogeneity was found (I2 = 0, p > 0.10). This protective effect of CCBs on the risk of active tuberculosis remained independent of the type of patient (with diabetes mellitus vs. general population) or the class of CCB administered (DHP-CCB vs. non-DHP-CCB) (test for subgroup differences I2 = 0, p > 0.10). However, this beneficial effect was more significant among the general population (RR 0.70; 95% CI 0.66–0.74) compared to patients with diabetes mellitus (RR 0.72; 95% CI 0.61–0.86) and among those patients treated with DHP-CCBs (RR 0.69; 95% CI 0.63–0.74) compared to patients treated with non-DHP-CCBs (RR 0.72; 95% CI 0.67–0.78).Conclusion: CCBs may reduce the risk of active TB in patients with diabetes and the general population. On the contrary, CCBs do not seem to have a protective effect on tuberculosis-related mortality. However, more evidence is still needed. We recommend developing clinical trials to verify these findings, including more diverse populations.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=352129]

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Effect of calcium-channel blockers on the risk of active tuberculosis and mortality: systematic review and meta-analysis

Meregildo-Rodriguez,

Asmat-Rubio,

Bardales-Zuta

et al. 2024

Front. Pharmacol.

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“…Parihar et al reported that M. tuberculosis growth was significantly reduced in human mononuclear cells and macrophages isolated from patients with familial hypercholesterolemia undergoing statin therapy, when compared with healthy donors (Parihar et al, 2014). Moreover, an epidemiological study showed that the cumulative use of statins and antibiotics was associated with a lower probability of developing pulmonary tuberculosis (Liao et al, 2017), and a meta-analysis underlined that statins may reduce the risk of active tuberculosis; however, heterogeneity and quality of evidence make any interpretation cautious (Meregildo-Rodriguez et al, 2022). Our understanding of cholesterol's role in M. ulcerans infection remains limited.…”

Section: Discussionmentioning

confidence: 99%

Repurposing of statins for Buruli Ulcer treatment: antimicrobial activity against Mycobacterium ulcerans

Dominguez,

Mendes,

Pacheco

et al. 2023

Front. Microbiol.

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Mycobacterium ulcerans causes Buruli Ulcer, a neglected infectious skin disease that typically progresses from an early non-ulcerative lesion to an ulcer with undermined edges. If not promptly treated, these lesions can lead to severe disfigurement and disability. The standard antibiotic regimen for Buruli Ulcer treatment has been oral rifampicin combined with intramuscular streptomycin administered daily for 8 weeks. However, there has been a recent shift toward replacing streptomycin with oral clarithromycin. Despite the advantages of this antibiotic regimen, it is limited by low compliance, associated side effects, and refractory efficacy for severe ulcerative lesions. Therefore, new drug candidates with a safer pharmacological spectrum and easier mode of administration are needed. Statins are lipid-lowering drugs broadly used for dyslipidemia treatment but have also been reported to have several pleiotropic effects, including antimicrobial activity against fungi, parasites, and bacteria. In the present study, we tested the susceptibility of M. ulcerans to several statins, namely atorvastatin, simvastatin, lovastatin and fluvastatin. Using broth microdilution assays and cultures of M. ulcerans-infected macrophages, we found that atorvastatin, simvastatin and fluvastatin had antimicrobial activity against M. ulcerans. Furthermore, when using the in vitro checkerboard assay, the combinatory additive effect of atorvastatin and fluvastatin with the standard antibiotics used for Buruli Ulcer treatment highlighted the potential of statins as adjuvant drugs. In conclusion, statins hold promise as potential treatment options for Buruli Ulcer. Further studies are necessary to validate their effectiveness and understand the mechanism of action of statins against M. ulcerans.

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“…In vivo murine models of chronic TB provided convincing evidence of statin’s effect and mechanism of action—the time to achieve TB-negative lungs under statin treatment shortened notably [ 108 ]. Statins were subjected to clinical trials based on their suspected in vivo effectivity in TB patients, and these trials showed that statin therapy may decrease TB incidence among diabetic and non-diabetic patients [ 109 , 110 ].…”

Section: Antibacterial Effects Of Statinsmentioning

confidence: 99%

Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance

Schelz,

Muddather,

Zupkó

2023

Antibiotics

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Efflux pump (EP)-mediated multidrug resistance (MDR) seems ubiquitous in bacterial infections and neoplastic diseases. The diversity and lack of specificity of these efflux mechanisms raise a great obstacle in developing drugs that modulate efflux pumps. Since developing novel chemotherapeutic drugs requires large investments, drug repurposing offers a new approach that can provide alternatives as adjuvants in treating resistant microbial infections and progressive cancerous diseases. Hydroxy-methyl-glutaryl coenzyme-A (HMG-CoA) reductase inhibitors, also known as statins, are promising agents in this respect. Originally, statins were used in the therapy of dyslipidemia and for the prevention of cardiovascular diseases; however, extensive research has recently been performed to elucidate the functions of statins in bacterial infections and cancers. The mevalonate pathway is essential in the posttranslational modification of proteins related to vital eukaryotic cell functions. In this article, a comparative review is given about the possible role of HMG-CoA reductase inhibitors in managing diseases of bacterial and neoplastic origin. Molecular research and clinical studies have proven the justification of statins in this field. Further well-designed clinical trials are urged to clarify the significance of the contribution of statins to the lower risk of disease progression in bacterial infections and cancerous diseases.

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Further insights into to the role of statins against active tuberculosis: systematic review and meta-analysis

Cited by 5 publications

References 29 publications

Effect of calcium-channel blockers on the risk of active tuberculosis and mortality: systematic review and meta-analysis

Effect of calcium-channel blockers on the risk of active tuberculosis and mortality: systematic review and meta-analysis

Repurposing of statins for Buruli Ulcer treatment: antimicrobial activity against Mycobacterium ulcerans

Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance

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